This program project grant is for basic and clinical studies on the pathogenesis and prevention of osteoporosis. It includes a core facility for administration, clinical services, and data processing and a core histomorphometric laboratory. Five major projects will be undertaken which will include studies on the possible mechanism of action of estrogen in bone and the role of prostaglandins, cytokines, and growth factors, studies on the effect of glucocorticoids on bone cell function, and exploration of the genetic determinants of osteoporosis, and a clinical comparison of exercise and estrogen for the prevention of postmenopausal bone loss. Pilot projects in the first year will examine racial differences in bone mass and morphology, the effects of scoliosis on bone mass, and methods for the immortalization of bone cells. This program project will be integrated with ongoing research efforts in the area of bone metabolism currently carried out with NIH support by a number of the investigators listed above as well as other scientists at the University of Connecticut Health Center.